Curindolizine, an Anti-Inflammatory Agent Assembled via Michael Addition of Pyrrole Alkaloids Inside Fungal Cells

<i>Curvularia</i> sp. IFB-Z10, a white croaker-associated fungus, generates a skeletally unprecedented indolizine alkaloid named curindolizine (<b>1</b>), which displays an anti-inflammatory action in lipopolyssacharide (LPS)-induced RAW 264.7 macrophages with an IC₅₀ value of 5.31 ± 0.21 μM. The enzymatic transformation test demonstrated that the unique curindolizine architecture was most likely produced by the regiospecific in-cell Michael addition reaction between pyrrole alkaloids, curvulamine, and 3,5-dimethylindolizin-8­(5<i>H</i>)-one

Muta-mycosynthesis of Naphthalene Analogs

A mutasynthetic strategy is introduced for the mycosynthesis of naphthalene-based molecules (mutadalesols A–F) with directed substitution patterns and new frameworks by generating and using the <i>ΔpksTL</i> mutant strain of <i>Daldinia eschscholzii.</i> (±)-Mutadalesol A and its (+)-enantiomer are cytotoxic, and its (−)-enantiomer inhibits Toll-like receptor 5 (TLR5). The in-culture reactability of fungal oligoketide intermediates with 5-aminonaphthalen-1-ol (ANL) is demonstrated, shedding light on bioorthogonal accesses to unnatural molecule libraries valuable in drug discovery pipelines

Discovery, Biosynthesis, and Heterologous Production of Streptoseomycin, an Anti-Microaerophilic Bacteria Macrodilactone

Streptoseomycin (<b>1</b>), which is a rare macrodilactone with potent activities against microaerophilic bacteria, featuring a pentacyclic 5/14/10/6/6 ring system together with an ether bridge, was characterized by a combination of spectroscopic method and X-ray analysis from a marine <i>Streptomyces seoulensis</i>. Sequencing and characterization of a ∼76-kb biosynthetic gene cluster led to the proposition of the biosynthetic pathway of <b>1</b>. Heterologous expression of the gene cluster using a BAC vector in <i>Streptomyces chartreusis</i> 1018 led to the successful production of <b>1</b>